Coronary Vasodilator Reserve Research Articles

Histopathologic Validation of Stress T1 Mapping in Myocardial Ischemia: Another Step toward Clinical Translation?

Histopathologic Validation of Stress T1 Mapping in Myocardial Ischemia: Another Step toward Clinical Translation?

Cardiac transplant and exercise cardiac rehabilitation.

Cardiac transplantation is the final therapeutic option for patients with end-stage heart failure. Most patients experience a favorable functional ability post-transplant. However, episodes of acute rejection, and multiple comorbidities such as hypertension, diabetes mellitus, chronic kidney disease and cardiac allograft vasculopathy are common. The number of transplants has increased steadily over the past two decades with 3,817 operations performed in the United States in 2021. Patients have abnormal exercise physiologic responses related to surgical cardiac denervation, diastolic dysfunction, and the legacy of reduced skeletal muscle oxidative capacity and impaired peripheral and coronary vasodilatory reserve resulting from pre-transplant chronic heart failure. Cardiorespiratory fitness is below normal for most patients with a mean peak VO2 of approximately 60% of predicted for healthy persons. Cardiac transplant recipients are therefore excellent candidates for Exercise-Based Cardiac Rehabilitation (CR). CR is safe and is a recommendation of professional societies both before (pre-rehabilitation) and after transplantation. CR improves peak VO2, autonomic function, quality of life, and skeletal muscle strength. Exercise training reduces the severity of cardiac allograft vasculopathy, stroke risk, percutaneous coronary intervention, hospitalization for either acute rejection or heart failure, and death. However, there are deficits in our knowledge regarding CR for women and children. In addition, the use of telehealth options for the provision of CR for cardiac transplant patients requires additional investigation.

Exhaustion of coronary vasodilatory reserve in the resting state: Clinical characteristics and long-term outcomes after intervention.

Resting coronary blood flow approximates flow with maximal vasodilation in very severe coronary stenosis. We studied the incidence of exhausted vasodilatory reserve by FFR, its clinical characteristics and long-term prognosis after FFR guided percutaneous coronary intervention (PCI). Consecutive patients undergoing FFR-guided PCI for coronary stenosis with reduced resting blood flow (baseline Pd/Pa < 0.8) were included. Basal maximal vasodilation (BMV) was defined as less than 5% difference between resting Pd/Pa and FFR, that is, FFR-baseline Pd/Pa < 0.05. Of 658 vessels that underwent FFR-guided PCI in 602 patients, 151 vessels had resting blood flow in the ischemic range (baseline Pd/Pa ≤ 0.8) and were included in the analysis. Of these, 28 lesions in 28 patients met criteria for BMV (4.25% of the entire registry and 18.5% of those with the reduced basal coronary flow). Stenosis severity was a significant predictor of the presence of BMV. In long term follow-up (median 106 ± 3.6months), BMV was not associated with increased target vessel revascularization (TVR) or major adverse cardiac event compared to non-BMV(OR 1.9, 95% CI 0.7-4.8, p-value 0.2 and OR 1.3, 95% CI 0.75-2.5, p=0.3, respectively). Low baseline Pd/Pa that approximates fractional flow reserve (exhausted vasodilatory reserve) defines a subgroup of patients with severe coronary artery stenosis. Prognosis, when treated with PCI along with medical therapy, appears similar to those with intact vasodilatory reserve.

Impaired Coronary Vasodilator Reserve and Adverse Prognosis in Patients With Systemic Inflammatory Disorders

ObjectivesThe purpose of this study was to evaluate the prognostic value of quantitative myocardial blood flow (MBF) and myocardial flow reserve (MFR), reflecting the integrated effects of diffuse atherosclerosis and microvascular dysfunction in patients with systemic inflammatory disorders. BackgroundRheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and psoriasis (PsO) are common inflammatory conditions with excess cardiovascular (CV) risk compared to the general population. Systemic inflammation perturbs endothelial function and has been linked to coronary vasomotor dysfunction. However, the prognostic significance of this vascular dysfunction is not known. MethodsThis was a retrospective study of patients with RA, SLE, and PsO undergoing clinically indicated rest and stress myocardial perfusion positron emission tomography (PET). Patients with an abnormal myocardial perfusion study or left ventricular dysfunction were excluded. MFR was calculated as the ratio of myocardial blood flow (MBF, ml/min/g) at peak stress compared to that at rest. ResultsAmong the 198 patients (median age: 65 years; 80% female), 20.7% had SLE, 31.8% had PsO, and 47.5% had RA. There were no differences in mean MFR between these conditions. Over a median follow-up of 7.8 years, there were 51 deaths and 63 major adverse cardiovascular events (MACE). Patients in the lowest tertile (MFR <1.65) had higher all-cause mortality than the highest tertile, which remained significant after adjusting for age, sex, and the pre-test clinical risk score (hazard ratio [HR]: 2.4; 95% confidence interval [CI]: 1.05 to 5.4; p = 0.038). Similarly, compared to the highest MFR tertile, those in the lowest tertile had a lower MACE-free survival after adjusting for age, sex, and the pre-test clinical risk score (HR: 3.6; 95% CI: 1.7 to 7.6; p = 0.001). ConclusionsIn patients with systemic inflammatory disorders, impaired coronary vasodilator reserve was associated with worse cardiovascular outcomes and all-cause mortality.

Chronic interval exercise training prevents BKCa channel-mediated coronary vascular dysfunction in aortic-banded miniswine.

Conventional treatments have failed to improve the prognosis of heart failure with preserved ejection fraction (HFpEF) patients. Thus, the purpose of this study was to determine the therapeutic efficacy of chronic interval exercise training (IT) on large-conductance Ca2+-activated K+ (BKCa) channel-mediated coronary vascular function in heart failure. We hypothesized that chronic interval exercise training would attenuate pressure overload-induced impairments to coronary BKCa channel-mediated function. A translational large-animal model with cardiac features of HFpEF was used to test this hypothesis. Specifically, male Yucatan miniswine were divided into three groups ( n = 7/group): control (CON), aortic banded (AB)-heart failure (HF), and AB-interval trained (HF-IT). Coronary blood flow, vascular conductance, and vasodilatory capacity were measured after administration of the BKCa channel agonist NS-1619 both in vivo and in vitro in the left anterior descending coronary artery and isolated coronary arterioles, respectively. Skeletal muscle citrate synthase activity was decreased and left ventricular brain natriuretic peptide levels increased in HF vs. CON and HF-IT animals. A parallel decrease in NS-1619-dependent coronary vasodilatory reserve in vivo and isolated coronary arteriole vasodilatory responsiveness in vitro were observed in HF animals compared with CON, which was prevented in the HF-IT group. Although exercise training prevented BKCa channel-mediated coronary vascular dysfunction, it did not change BKCa channel α-subunit mRNA, protein, or cellular location (i.e., membrane vs. cytoplasm). In conclusion, these results demonstrate the viability of chronic interval exercise training as a therapy for central and peripheral adaptations of experimental heart failure, including BKCa channel-mediated coronary vascular dysfunction. NEW & NOTEWORTHY Conventional treatments have failed to improve the prognosis of heart failure with preserved ejection fraction (HFpEF) patients. Our findings show that chronic interval exercise training can prevent BKCa channel-mediated coronary vascular dysfunction in a translational swine model of chronic pressure overload-induced heart failure with relevance to human HFpEF.

Coronary vasomotor function in infarcted and remote myocardium after primary percutaneous coronary intervention

ObjectiveIn patients with acute myocardial infarction (AMI), coronary vasomotor function is impaired in the myocardial territory supplied by the culprit artery and in remote myocardium supplied by angiographically normal vessels....

Impact of Aortic Valve Stenosis on Coronary Hemodynamics and the Instantaneous Effect of Transcatheter Aortic Valve Implantation.

Aortic valve stenosis (AS) induces compensatory alterations in left ventricular hemodynamics, leading to physiological and pathological alterations in coronary hemodynamics. Relief of AS by transcatheter aortic valve implantation (TAVI) decreases ventricular afterload and is expected to improve microvascular function immediately. We evaluated the effect of AS on coronary hemodynamics and the immediate effect of TAVI. Intracoronary pressure and flow velocity were simultaneously assessed at rest and at maximal hyperemia in an unobstructed coronary artery in 27 patients with AS before and immediately after TAVI and in 28 patients without AS. Baseline flow velocity was higher and baseline microvascular resistance was lower in patients with AS as compared with controls, which remained unaltered post-TAVI. In patients with AS, hyperemic flow velocity was significantly lower as compared with controls (44.5±14.5 versus 54.3±18.6 cm/s; P=0.04). Hyperemic microvascular resistance (expressed in mm Hg·cm·s(-1)) was 2.10±0.69 in patients with AS as compared with 1.80±0.60 in controls (P=0.096). Coronary flow velocity reserve in patients with AS was lower, 1.9±0.5 versus 2.7±0.7 in controls (P<0.001). Improvement in coronary hemodynamics after TAVI was most pronounced in patients without post-TAVI aortic regurgitation. In these patients (n=20), hyperemic flow velocity increased significantly from 46.24±15.47 pre-TAVI to 56.56±17.44 cm/s post-TAVI (P=0.003). Hyperemic microvascular resistance decreased from 2.03±0.71 to 1.66±0.45 (P=0.050). Coronary flow velocity reserve increased significantly from 1.9±0.4 to 2.2±0.6 (P=0.009). The vasodilatory reserve capacity of the coronary circulation is reduced in AS. TAVI induces an immediate decrease in hyperemic microvascular resistance and a concomitant increase in hyperemic flow velocity, resulting in immediate improvement in coronary vasodilatory reserve.

Abstract 19312: A Follow-up Study of Coronary Vasomotor Function in Ischemic and Remote Myocardium Following Successful Percutaneous Revascularization for Acute Myocardial Infarction - a [15O]H2O PET Study

Introduction: In patients with acute myocardial infarction (AMI), coronary vasomotor function is not only impaired in the myocardial territory supplied by the culprit-artery but also in remote myocardium supplied by angiographically normal vessels. Aims: The aim was to investigate the temporal evolution of coronary vasodilatory reserve in patients with AMI by use of [15O]H2O PET, after successful percutaneous coronary intervention (PCI). Methods: Fourty-four patients with AMI and successful revascularization by PCI were included (i.e. TIMI II or III flow after coronary stenting). Subjects were examined one week and three months after AMI with [15O]H2O PET to assess the coronary flow reserve (CFR). CFR was defined as the ratio of myocardial blood flow during hyperemia (hMBF) and rest (MBF). Additionally, 45 age and sex matched subjects without a prior cardiac history underwent similar scanning procedures and served as a control group. Results: At baseline, CFR averaged 1.77 ± 0.63 in infarcted myocardium versus 2.41 ± 0.79 in remote myocardium (p &lt; 0.001). In comparison, CFR in the control group averaged 4.16 ± 1.45 (p = 0.001 versus both). During follow-up, the CFR increased from 1.77 ± 0.63 to 2.75 ± 0.89 in infarcted myocardium (p &lt; 0.001), and from 2.41 ± 0.79 to 2.85 ± 0.75 in remote myocardium (p = 0.001). This was predominantly due to an increase in hMBF, from 1.64 ± 0.54 to 2.19 ± 0.74 mL/min/g in infarcted myocardium (p &lt; 0.001), and 2.20 ± 0.56 to 2.61 ± 0.65 mL/min/g in remote myocardium (p = 0.001). Conclusions: Coronary vasodilatory reserve is impaired in both ischemic and remote myocardium directly after AMI. Following successful revascularization, the coronary vasodilatory reserve significantly improved in both regions. As a consequence, these early and late post-infarct alterations in remote myocardium may also affect temporal infarct evolution and recovery of left ventricular function.

Exercise Hemodynamics and Risk Assessment in Asymptomatic Aortic Stenosis

More than half a century ago, in the American Journal of Cardiology , Dr Paul Wood aptly described aortic stenosis (AS) as “a simple mechanical fault which, if severe enough, imposes a heavy burden on the left ventricle and sooner or later overcomes it.”1 Our subsequent understanding of the pathophysiology of AS, using more sophisticated tools than those at Dr Wood's disposal, has confirmed his concept. Severe chronic pressure overload and outflow obstruction beget left ventricular (LV) hypertrophy and its attendant myocardial fibrosis and impaired coronary vasodilator reserve, leading to LV systolic and diastolic dysfunction, and progressing ultimately to the anticipated symptoms of dyspnea, angina, and presyncope or syncope, which are harbingers of death within a few years. Once symptoms develop, the treatment strategy is clear, because aortic valve replacement (AVR) improves symptoms, improves LV function, and improves survival. The indications for AVR in asymptomatic patients, however, remain less clear and the subject of ongoing debate.2–4 Although the current evidence-based guidelines recommend a watchful waiting approach for most patients, with no class I indications for surgery in asymptomatic patients with normal LV systolic function,5,6 numerous studies have shown that patients with severe AS have a high likelihood of developing symptoms and requiring surgery within 3 to 5 years,7–10 and some series have reported that asymptomatic patients with severe AS are also at risk of death when managed without surgery.11,12 Because the operative risk of AVR is low in experienced centers,11,13 there is intense interest in identifying the subsets of asymptomatic patients that have the highest likelihood of dying or developing symptoms over the short term and that might benefit from early, preemptive AVR rather than a watchful waiting approach. Article see p 851 Determining …

In Response

It was not our intention to discuss the details of coronary microvascular control, because the focus of our reviews was on the effects of receptors throughout the circulation.1,2 Dr. Crystal3 and others4 have shown that to variable degrees, the myocardium is capable of regulating oxygen supply in response to changes in demand, an ability not unique to the myocardium.5 Like all organs capable of autoregulation, when demand is excessive or supply too scarce, autoregulation fails. This phenomenon is the primary interest of our manuscripts, and this inability to autoregulate ad infinitum has been shown in multiple organ systems. Our allusion to Dr. Antonopoulos's manuscript6 was for the sake of completeness; we acknowledged the difficulty of interpreting this interesting manuscript and therefore supported its conclusions with 3 additional studies. Alpha-adrenergic agonists have differential end-organ effects. Few organs can autoregulate as efficiently as the heart, which likely explains its relative resistance to changes in myocardial flow following α-adrenergic stimulation. As Dr. Crystal notes, when myocardial work is increased by systemic arteriolar constriction and a marked increase in blood pressure, the local autoregulation in the coronary microvasculature of healthy hearts can counterbalance increased α-adrenergic stimulation in these vessels, as demonstrated by his studies7 and others. We agree that the work of Dr. Crystal and others suggests potential mechanisms for this observation; whether this remains clinically significant in the face of significantly increased demand is unknown. However, various clinical studies suggest that in patients8 in whom coronary circulation is diseased at the level of the large or small vessels (e.g., mechanical or biochemical disruption of endothelial function; inflammatory activation within the vascular smooth muscle), the microcirculatory control may become imbalanced. Consequently, the statement “the myocardium is not at risk when phenylephrine is used to treat hypotension in patients with adequate cardiac function and coronary vasodilator reserve” must be viewed in the context of experimental work or the more ambiguous clinical setting. Edward C. Nemergut, MD Carl Lynch III, MD, PhD H. Thiele, MD Departments of Anesthesiology and Neurological Surgery University of Virginia Health System Charlottesville, VA Department of Anesthesiology Duke University Hospital Durham, NC [email protected]

Dietary fish oil preserves cardiac function in the hypertrophied rat heart

Regular fish or fish oil intake is associated with a low incidence of heart failure clinically, and fish oil-induced reduction in cardiac remodelling seen in hypertrophy models may contribute. We investigated whether improved cardiac energy efficiency in non-hypertrophied hearts translates into attenuation of cardiac dysfunction in hypertrophied hearts. Male Wistar rats (n 33) at 8 weeks of age were sham-operated or subjected to abdominal aortic stenosis to produce pressure-overload cardiac hypertrophy. Starting 3 weeks post-operatively to follow initiation of hypertrophy, rats were fed a diet containing 10 % olive oil (control) or 5 % fish oil (ROPUFA® 30 (17 % EPA, 10 % DHA))+5 % olive oil (FO diet). At 15 weeks post-operatively, ventricular haemodynamics and oxygen consumption were evaluated in the blood-perfused, isolated working heart. Resting and maximally stimulated cardiac output and external work were >60 % depressed in hypertrophied control hearts but this was prevented by FO feeding, without attenuating hypertrophy. Cardiac energy efficiency was lower in hypertrophy, but greater in FO hearts for any given cardiac mass. Coronary blood flow, restricted in hypertrophied control hearts, increased with increasing work in hypertrophied FO hearts, revealing a significant coronary vasodilator reserve. Pronounced cardiac dysfunction in hypertrophied hearts across low and high workloads, indicative of heart failure, was attenuated by FO feeding in association with membrane incorporation of n-3 PUFA, principally DHA. Dietary fish oil may offer a new approach to balancing the high oxygen demand and haemodynamic requirements of the failing hypertrophied heart independently of attenuating hypertrophy.

Effects of alcohol septal ablation on coronary microvascular function and myocardial energetics in hypertrophic obstructive cardiomyopathy

This study investigated the effects of alcohol septal ablation (ASA) on microcirculatory function and myocardial energetics in patients with hypertrophic cardiomyopathy (HCM) and left ventricular outflow tract (LVOT) obstruction. In 15 HCM patients who underwent ASA, echocardiography was performed before and 6 mo after the procedure to assess the LVOT gradient (LVOTG). Additionally, [(15)O]water PET was performed to obtain resting myocardial blood flow (MBF) and coronary vasodilator reserve (CVR). Changes in LV mass (LVM) and volumes were assessed by cardiovascular magnetic resonance imaging. Myocardial oxygen consumption (MVo(2)) was evaluated by [(11)C]acetate PET in a subset of seven patients to calculate myocardial external efficiency (MEE). After ASA, peak LVOTG decreased from 41 ± 32 to 23 ± 19 mmHg (P = 0.04), as well as LVM (215 ± 74 to 169 ± 63 g; P < 0.001). MBF remained unchanged (0.94 ± 0.23 to 0.98 ± 0.15 ml·min(-1)·g(-1); P = 0.45), whereas CVR increased (2.55 ± 1.23 to 3.05 ± 1.24; P = 0.05). Preoperatively, the endo-to-epicardial MBF ratio was lower during hyperemia compared with rest (0.80 ± 0.18 vs. 1.18 ± 0.15; P < 0.001). After ASA, the endo-to-epicardial hyperemic (h)MBF ratio increased to 1.03 ± 0.26 (P = 0.02). ΔCVR was correlated to ΔLVOTG (r = -0.82; P < 0.001) and ΔLVM (r = -0.54; P = 0.04). MEE increased from 15 ± 6 to 20 ± 9% (P = 0.04). Coronary microvascular dysfunction in obstructive HCM is at least in part reversible by relief of LVOT obstruction. After ASA, hMBF and CVR increased predominantly in the subendocardium. The improvement in CVR was closely correlated to the absolute reduction in peak LVOTG, suggesting a pronounced effect of LV loading conditions on microvascular function of the subendocardium. Furthermore, ASA has favorable effects on myocardial energetics.

Myocardial Bridging

According to postmortem studies, coronary atherosclerosis can be substantial and reach a high prevalence of advanced lesions, including atheroma and fibroatheroma in young adults.1,2 Risk factors associated with coronary atherosclerosis such as dyslipidemia, smoking, diabetes mellitus, and hypertension have been identified. The development of atherosclerosis seems to be related to the magnitude and duration of exposure.3 Although research concentrates on identifying genetic markers in genome-wide association studies, there is still a lack of knowledge about the individual risk of developing coronary atherosclerosis.4 When atherosclerosis presents as acute coronary syndromes, mortality may be high.5 Plaque rupture and erosion have been identified as major underlying pathological-anatomic characteristics,6 but some suspect other mechanisms.7 In this issue of Circulation , Ishikawa et al8 present evidence that myocardial bridging may play a role as a congenital anatomic risk factor for coronary atherosclerosis and myocardial infarction. Article see p 376 Myocardial bridging results when myocardial tissue covers part of the left anterior descending coronary artery, resulting in a tunneled arterial segment, which can be regarded as a congenital variant.9–11 The prevalence is reported to be >50% at autopsy.12 Clinically, the diagnosis of myocardial bridging is established by coronary angiography demonstrating a systolic compression, described as a “milking effect,”13 but it was present in only <5% of cases recently in a large number of Chinese patients.14 When nitroglycerin was used as …

Altered Mechanism of Adenosine-Induced Coronary Arteriolar Dilation in Early-Stage Metabolic Syndrome

Onset of the combined metabolic syndrome (MetS) is a complex progressive process involving numerous cardiovascular risk factors. Although patients with established MetS exhibit reduced coronary flow reserve and individual components of the MetS reduce microvascular vasodilation, little is known concerning the impact of early-stage MetS on the mechanisms of coronary flow control. Therefore, we tested the hypothesis that coronary arteriolar dilation to adenosine is attenuated in early-stage MetS by reduced A2 receptor function and diminished K+ channel involvement. Pigs were fed control or high-fat/cholesterol diet for 9 weeks to induce early-stage MetS. Coronary atheroma was determined in vivo with intravascular ultrasound. In vivo coronary dilation was determined by intracoronary adenosine infusion. Further, apical coronary arterioles were isolated, cannulated and pressurized to 60 cmH2O for in vitro pharmacologic assessment of adenosine dilation. Coronary atheroma was not different between groups, indicating early-stage MetS. Coronary arteriolar dilation to adenosine (in vivo) and 2-chloroadenosine (2-CAD; in vitro) was similar between groups. In control arterioles, 2-CAD-mediated dilation was reduced only by selective A(2A) receptor inhibition, whereas only dual A(2A/2B) inhibition reduced this response in MetS arterioles. Arteriolar A(2B), but not A(2A), receptor protein expression was reduced by MetS. Blockade of voltage-dependent K+ (K(v)) channels reduced arteriolar sensitivity to 2-CAD in both groups, whereas ATP-sensitive K+ (K(ATP)) channel inhibition reduced sensitivity only in control arterioles. Our data indicate that the mechanisms mediating coronary arteriolar dilation to adenosine are altered in early-stage MetS prior to overt decrements in coronary vasodilator reserve.

P-160 Potentiated Angiogenetic Effects of LOX-1 via Induction of Vascular Endothelial Growth Factor in Ischemic Leg

periodic acceleration alleviates myocardial ischemia as a result of increased coronary and peripheral vasodilatory reserve. Methods: Twenty one anginal patients [66±10 (SD) years] were randomly assigned to remain sedentary (Sedentary group: SE group, n = 9) or undergo 20 passive exercise sessions with the motion platform for 4 weeks (Periodic acceleration group: PA group, n = 10). Periodic acceleration was applied at 2 to 3Hz and approximately ±2.2m/sec2 for 45 min. We repeated the symptom-limited exercise test using the standard Bruce protocol and adenosine sestamibi myocardial scintigraphy. Results: Treatment with periodic acceleration increased the extent of improvement in exercise time until 0.1mV ST depression from pre-treatment to post-treatment (PA group vs. SE group = 2.1±1.1 vs. 0.4±0.9 minutes, p < 0.05), and the extent of improvement in double product at 0.1mV ST depression (PA group vs. SE group = 1,950±1,101mmHgbeats/min vs. 875±1,378mmHg-beats/min, p < 0.05). After treatment with periodic acceleration, the extent of improvement in severity score of the scintigraphy during adenosine infusion was significantly higher in PA group compared with SE group (6.1±4.7 to 1.4±2.8, p < 0.05), indicating that size of ischemic and hibernating myocardium became smaller with treatment. The extent of decrease in left ventricular end-diastolic volume index were significantly higher in PA group compared with SE group (15.1±17.4 to 0.1±2.0ml/m2, p < 0.05), with a significantly augmented extent of improvement in left ventricular ejection fraction (4.3±5.1 to 0.1±2.1%, p < 0.05). Conclusions: Novel treatment with an application of repeated periodic acceleration improves myocardial ischemia and left ventricular function in anginal patients through central and peripheral effects.

Invited Commentary

In myocardial contrast echocardiography (MCE), microscopic particles of gas-filled aqueous shells, which cause ultrasound reflections far stronger than those made by the native circulatory system, are injected intravenously. These microbubbles traverse the pulmonary circulation in sufficiently high concentration to cause contrast enhancement in the left ventricle [1Lang R.M. Mor-Avi V. Clinical utility of contrast-enhanced echocardiography.Clin Cardiol. 2006; 29: I-15-25Google Scholar]. Combined with other advancements in ultrasound imaging technologies, such as harmonic imaging and accelerated intermittent imaging, which improve the detection of contrast agents, MCE has been clinically used in the diagnosis and prognosis of coronary artery disease by assessing coronary artery flow and flow reserve [1Lang R.M. Mor-Avi V. Clinical utility of contrast-enhanced echocardiography.Clin Cardiol. 2006; 29: I-15-25Google Scholar, 2Caiati C. Montaldo C. Zedda N. Bina A. Illiceto S. New noninvasive method for coronary flow reserve assessment: contrast-enhanced transthoracic second harmonic echo Doppler.Circulation. 1999; 99: 771-778Crossref PubMed Scopus (297) Google Scholar, 3Mulvagh S.L. Foley D.A. Aeschbacher B.C. Klarich K.W. Seward J.B. Second harmonic imaging of intravenously administered echocardiographic contrast: visualization of coronary arteries and measurement of coronary blood flow.J Am Coll Cardiol. 1996; 27: 1519-1529Abstract Full Text PDF PubMed Scopus (122) Google Scholar]. Miyagawa and colleagues [4Miyagawa S. Masai T. Fukuda H. et al.Coronary microcirculatory dysfunction in aortic stenosis: myocardial contrast echocardiography study.Ann Thorac Surg. 2009; 87: 715-719Abstract Full Text Full Text PDF PubMed Scopus (19) Google Scholar] report on the use of MCE to assess microcirculatory dysfunction before and after aortic valve replacement (AVR) in 22 patients with isolated moderate or severe AS. Compared with the contrast intensity (CI) of the ventricular cavity, the CI of the subendocarial region was −18.46 dB in patients with AS, versus −11.8 dB and −12.68 dB in controls, thereby demonstrating significantly reduced myocardial blood flow. Post-AVR, subendocardial blood flow improved to −13 dB and −12.7 dB at 2 weeks and 1 year, respectively. Subepicardial blood flow did not change post-AVR. It is known [5Hildick-Smith D.J.R. Shapiro L.M. Coronary flow reserve improves after aortic valve replacement for aortic stenosis: an adenosine transthoracic echocardiography study.J Am Coll Cardiol. 2000; 36: 1889-1896Abstract Full Text Full Text PDF PubMed Scopus (100) Google Scholar, 6Rajappan K. Rimoldi O.E. Camici P.G. Bellenger N.G. Pennell D.J. Sheridan D.J. Functional changes in coronary microcirculation after valve replacement in patients with aortic stenosis.Circulation. 2003; 107: 3170-3175Crossref PubMed Scopus (173) Google Scholar] that it is the hyperemic MBF (post-adenosine or dipyrimadole) and not the resting MBF that is increased after AVR. Because coronary vasodilator reserve (CVR) is the ratio of hyperemic to resting MBF, CVR increases post-AVR. Also, CVR improved before ventricular mass regression was completed, suggesting an important role for diastolic perfusion time improvement with AVR. Herein lies the major criticism of this study. The MBF is mainly diastolic in nature, and calculations of CVR are based on diastolic flows or flow velocity. The authors, on the other hand have used end-systolic measurements of MBF. The relevance as well as the significance of end-systolic MBF measurements will remain controversial. It would have been desirable if the authors had compared MCE with other modalities such as positron emission tomography to assess MBF. However, the use of MCE has many advantages in comparison with routine echocardiography as previously mentioned. The authors are to be commended for this ingenious use of MCE. If indeed it can reliably measure CVR in AS patients, it would be very interesting to follow asymptomatic patients with AS by MCE to see if CVR measurements correlate with development of symptoms or the need for surgery. Coronary Microcirculatory Dysfunction in Aortic Stenosis: Myocardial Contrast Echocardiography StudyThe Annals of Thoracic SurgeryVol. 87Issue 3PreviewThe aims of this study were to quantify the microcirculatory dysfunction in aortic stenosis (AS) and to measure the changes in transmural perfusion after aortic valve replacement (AVR), using quantitative myocardial contrast echocardiography. Full-Text PDF

Age impairs Flk-1 signaling and NO-mediated vasodilation in coronary arterioles

Impairment of flow-induced vasodilation in coronary resistance arterioles may contribute to the decline in coronary vasodilatory reserve that occurs with advancing age. This study investigated the effects of age on flow-induced signaling and activation of nitric oxide (NO)-mediated vasodilation in coronary resistance arterioles. Coronary arterioles were isolated from young (approximately 6 mo) and old (approximately 24 mo) male Fischer-344 rats to assess vasodilation to flow, vascular endothelial growth factor (VEGF), and ACh. Flow- and VEGF-induced vasodilation of coronary arterioles was impaired with age (P<or=0.05); however, ACh-induced vasodilation was preserved with age. NG-nitro-L-arginine methyl ester (L-NAME) (1x10(-5) M) eliminated vasodilation to flow, VEGF, and ACh, indicating dependence of these responses on NO. SU-1498, an inhibitor of vascular endothelial growth factor receptor 2 (VEGFR, also known as Flk-1), abolished age-related differences in flow-induced vasodilation. Flow-stimulated phosphorylation of Flk-1 in coronary arterioles from young but not old rats and Flk-1 protein was reduced in coronary arterioles from old rats compared with those from young rats. Flow stimulated phosphorylation of endothelial nitric oxide synthase (eNOS) in coronary arterioles from both young and old rats. VEGF induced phosphorylation of both protein kinase B (Akt) and eNOS in coronary arterioles. VEGF-induced phosphorylation of Akt, but not eNOS, was significantly reduced in arterioles from old rats compared with arterioles from young rats. Wortmannin, an inhibitor of phosphatidylinositol (PI) 3-kinase, eliminated age-related differences in both flow- and VEGF-induced vasodilation. These results indicate that impairment of Flk-1/PI3-kinase signaling contributes to the reduction of flow-induced vasodilation in coronary arterioles with advancing age.

Quantitative relationship between coronary vasodilator reserve assessed by 82Rb PET imaging and coronary artery stenosis severity

The relationship between myocardial blood flow (MBF) and stenosis severity has been determined previously using cyclotron-produced radiotracers such as (15)O-H(2)O and (13)N-ammonia. An attractive alternative to overcome the limitations related to the use of cyclotron might be to use the generator-produced (82)Rb as a flow tracer. The current study was undertaken to investigate the relationship between MBF and coronary vasodilator reserve (CVR) as measured by (82)Rb positron emission tomography (PET) and the percent diameter stenosis as defined by quantitative coronary arteriography. We prospectively evaluated 22 individuals: 15 patients (60 +/- 11 years of age) with angiographically documented coronary artery disease (CAD) and seven age-matched (56 +/- 9 years) asymptomatic individuals without risk factors for CAD. Dynamic (82)Rb PET was performed at rest and after dipyridamole vasodilation. MBF, CVR and an index of 'minimal coronary resistance' (MCR) were assessed in each of the three main coronary territories. Rest and stress MBF in regions subtended by vessels with less than 50% diameter stenosis was similar to that of the individuals with no risk factors for CAD. As a result, CVR was also similar in the two groups (1.9, interquartile [IQ] range from 1.7 to 2.7 vs. 2.2, IQ range from 2 to 3.4 respectively, p = 0.09). CVR successfully differentiated coronary lesions with stenosis severity 70% to 89% from those with 50% to 69% stenosis (1, IQ range from 1 to 1.3 vs. 1.7, IQ range from 1.4 to 2), respectively, p = 0.001. In addition, hyperaemic MBF (r (2) = 0.74, p < 0.001), CVR (r (2) = 0.69, p < 0.001) and MCR (r (2) = 0.78, p < 0.001) measurements were inversely and non-linearly correlated to the percent diameter stenosis on angiography. MBF and CVR are inversely and non-linearly correlated to stenosis severity. Quantitative (82)Rb PET can be a clinically useful tool for an accurate functional assessment of CAD.

Diabetic Cardiomyopathy and Anesthesia

Diabetic Cardiomyopathy and Anesthesia

Stunning, Hibernation, and Assessment of Myocardial Viability

The last 3 decades have witnessed an unprecedented improvement in the outcome of patients with acute coronary syndromes. The widespread use of thrombolytic therapy and percutaneous coronary interventions, in association with increasingly potent antithrombotic agents, has contributed to significant reductions in mortality and morbidity in these patients. Although overall survival has improved, a downside of this success has been the greater number of patients with residual left ventricular (LV) dysfunction undergoing progressive LV remodeling and congestive heart failure. This problem is compounded by the rising age of our population and the higher prevalence of comorbidities such as diabetes mellitus that confer an increased risk of coronary artery disease (CAD) and congestive heart failure. Patients with CAD represent by far the most numerous cohort among those with congestive heart failure, and their treatment remains a partial success.1 Typically, these patients have multivessel disease, increased LV volumes, and variable degrees of regional and/or global systolic dysfunction, although more cases of isolated diastolic dysfunction have been reported recently.2–4 In these patients, coronary revascularization may lead to symptomatic and prognostic improvement, and these clinical benefits are accompanied by evidence of reverse LV remodeling. In this context, the concept of myocardial viability was developed and a number of different techniques have been used to demonstrate the presence of viable tissue before coronary revascularization. The aim of this review article is to summarize our current understanding of the concept of myocardial viability and its clinical implications in patients with CAD and chronic LV dysfunction. Throughout this review, we use the term viability to describe dysfunctional myocardium subtended by diseased coronary arteries with limited or absent scarring that therefore has the potential for functional recovery. Viability is a prospective definition, but it does not imply evidence of functional recovery after interventions. The term hibernation, which …